The major areas of effort in this project have been (1) To refine existing methodologies for the study of cortical functioning based on positron emission tomography (PET); (2) To develop new tracers or other approaches for the study of neurotransmitter function in normal and abnormal physiology; (3) To apply what tracer methodologies we have available to the study of neuropsychiatric disorders. To these ends the following achievements are notable. Our study of schizophrenic patients, on and off neuroleptics, receiving repeated somatosensory stimulation (SS) during metabolic measurement in comparison to normals by FDG-PET i.e., the study of regional brain activities through observations of regional glucose metabolic rates (lCMRglu's) as calculated from PET scan meaasurements of 18F-deoxyglucose accumulation has been completed and differences reported. This work provided weak support for the existence of "hypofrontality" in schizophrenia, and did not find any improvement in hypofrontality when patients were treated. We have completed the collection of data on the study of two additional behavioral paradigms with FDG-PET. These studies were of auditory continuous performance (CPT), and rest (REST) and totaled 43 normals. Altogether the data allowed us to develop a statistical approach to the handling of PET data that is both sensitive to the small changes observed upon behavioral changes while maintaining reliability. It provides evidence that SS may not be a good condition for observing hypofrontality except perhaps within one particular area of the frontal cortex. Most importantly, the data from this comparison strongly supports the heterogenity of the frontal cortex and the need to examine very carefully the detailed pattern of metabolism in the frontal cortex if we are to understand the physiology and pathophysiology of behavior.